Prognostic and predictive value of tumor deposits in advanced signet ring cell colorectal cancer: SEER database analysis and multicenter validation.

BACKGROUND: Colorectal signet-ring cell carcinoma (SRCC) is a rare cancer with a bleak prognosis. The relationship between its clinicopathological features and survival remains incompletely elucidated. Tumor deposits (TD) have been utilized to guide the N staging in the 8th edition of American Joint Committee on Cancer (AJCC) staging manual, but their prognostic significance remains to be established in colorectal SRCC. PATIENTS AND METHODS: The subjects of this study were patients with stage III/IV colorectal SRCC who underwent surgical treatment. The research comprised two cohorts: a training cohort and a validation cohort. The training cohort consisted of 631 qualified patients from the SEER database, while the validation cohort included 135 eligible patients from four independent hospitals in China. The study assessed the impact of TD on Cancer-Specific Survival (CSS) and Overall Survival (OS) using Kaplan-Meier survival curves and Cox regression models. Additionally, a prognostic nomogram model was constructed for further evaluation. RESULTS: In both cohorts, TD-positive patients were typically in the stage IV and exhibited the presence of perineural invasion (PNI) (P < 0.05). Compared to the TD-negative group, the TD-positive group showed significantly poorer CSS (the training cohort: HR, 1.87; 95% CI, 1.52-2.31; the validation cohort: HR, 2.43; 95% CI, 1.55-3.81; all P values < 0.001). This association was significant in stage III but not in stage IV. In the multivariate model, after adjusting for covariates, TD maintained an independent prognostic value (P < 0.05). A nomogram model including TD, N stage, T stage, TNM stage, CEA, and chemotherapy was constructed. Through internal and external validation, the model demonstrated good calibration and accuracy. Further survival curve analysis based on individual scores from the model showed good discrimination. CONCLUSION: TD positivity is an independent factor of poor prognosis in colorectal SRCC patients, and it is more effective to predict the prognosis of colorectal SRCC by building a model with TD and other clinically related variables.

The evaluation of synchronous and asynchronous online learning: student experience, learning outcomes, and cognitive load.

BACKGROUND: The abrupt onset of the COVID-19 pandemic compelled universities to swiftly establish online teaching and learning environments that were not only immediately deployable but also conducive to high-quality education. This study aimed to compare the effectiveness of the online synchronous and asynchronous teaching formats in the dermatology lecture for undergraduate medical students, including academic performance, self-efficacy, and cognitive load. METHODS: A total of 170 fourth-year undergraduate medical students attending the dermatology lecture were included. The lecture was delivered using both the synchronous method (live online lecture via Webex meeting) and the asynchronous method (lecture videos shared on YouTube). The students had the freedom to choose their preferred method of attending the online lecture. The study assessed three main aspects: (1) learning outcomes measured through pretest, posttest, and retention test scores; (2) cognitive load experienced by students, including mental load and mental effort measured using eight items; and (3) satisfaction levels with each online teaching format. RESULTS: In this study, 70 students opted for the synchronous online lecture, while 100 students chose the asynchronous online lecture. Both synchronous and asynchronous teaching methods exhibited significant improvements in post and retention test scores compared to the pretest. Satisfaction levels, rated on a scale of 0-5, were generally high for both teaching methods, with no significant differences observed (4.6 for synchronous, 4.53 for asynchronous; p =.350). Regarding cognitive load, the synchronous method showed a significantly lower level than the asynchronous method (p =.0001). Subgroup analysis revealed no difference in mental effort (p =.0662), but the level of mental load was lower in the synchronous method (p =.0005). CONCLUSIONS: Both synchronous and asynchronous online teaching methods demonstrated improvements in learning outcomes and high levels of student satisfaction. However, the cognitive load experienced by students was lower in the synchronous setting compared to the asynchronous setting. These findings remind health professions educators that they would consider the students' cognitive load when designing online curricula.

Globotriaosylsphingosine improves risk stratification of kidney progression in Fabry disease patients.

BACKGROUND: Kidney damage is common in patients with Fabry disease (FD), but more accurate information about the risk of progression to kidney failure is needed for clinical decision-making. In particular, FD patients with mild renal involvement often lack timely intervention and treatment. We aimed to utilize a model to predict the risk of renal progression in FD patients. METHODS: Between November 2011 and November 2019, ERT-naive patients with FD were recruited from three medical centers in China. To assess the risk of a 50% decline in the estimated glomerular filtration rate (eGFR) or end-stage kidney disease (ESKD), Cox proportional hazards models were utilized. The performance of these models was assessed using discrimination, calibration, and reclassification. RESULTS: A total of 117 individuals were enrolled. The mean follow-up time was 4.8 years, during which 35 patients (29.9 %) progressed to the composite renal outcomes. Male sex, baseline proteinuria, eGFR and globotriaosylsphingosine (Lyso-Gb3) were found to be independent risk factors for kidney progression by the Cox model, based on which a combined model containing those clinical variables and Lyso-Gb3 and clinical models including only clinical indicators were constructed. The two prediction models had relatively good performance, with similar model fit measured by R2 (59.8 % vs. 61.1 %) and AIC (51.54 vs. 50.08) and a slight increase in the C statistic (0.949 vs. 0.951). Calibration curves indicated closer alignment between predicted and actual renal outcomes in the combined model. Furthermore, subgroup analysis revealed that Lyso-Gb3 significantly improved the predictive performance of the combined model for kidney prognosis in low-risk patients with a baseline eGFR over 60 ml/min/1.73 m2 or proteinuria levels less than 1 g/d when compared to the clinical model. CONCLUSIONS: Lyso-Gb3 improves the prediction of kidney outcomes in FD patients with a low risk of progression, suggesting that these patients may benefit from early intervention to assist in clinical management. These findings need to be externally validated.

Bulk anda single-cell transcriptome profiling reveals the molecular characteristics of T cell-mediated tumor killing in pancreatic cancer.

Background: Despite the potential of immune checkpoint blockade (ICB) as a promising treatment for Pancreatic adenocarcinoma (PAAD), there is still a need to identify specific subgroups of PAAD patients who may benefit more from ICB. T cell-mediated tumor killing (TTK) is the primary concept behind ICB. We explored subtypes according to genes correlated with the sensitivity to TKK and unraveled their underlying associations for PAAD immunotherapies. Methods: Genes that control the responsiveness of T cell-induced tumor destruction (GSTTK) were examined in PAAD, focusing on their varying expression levels and association with survival results. Moreover, samples with PAAD were separated into two subsets using unsupervised clustering based on GSTTK. Variability was evident in the tumor immune microenvironment, genetic mutation, and response to immunotherapy among different groups. In the end, we developed TRGscore, an innovative scoring system, and investigated its clinical and predictive significance in determining sensitivity to immunotherapy. Results: Patients with PAAD were categorized into 2 clusters based on the expression of 52 GSTTKs, which showed varying levels and prognostic relevance, revealing unique TTK patterns. Survival outcome, immune cell infiltration, immunotherapy responses, and functional enrichment are also distinguished among the two clusters. Moreover, we found the CATSPER1 gene promotes the progression of PAAD through experiments. In addition, the TRGscore effectively predicted the responses to chemotherapeutics or immunotherapy in patients with PAAD and overall survival. Conclusions: TTK exerted a vital influence on the tumor immune environment in PAAD. A greater understanding of TIME characteristics was gained through the evaluation of the variations in TTK modes across different tumor types. It highlights variations in the performance of T cells in PAAD and provides direction for improved treatment approaches.

Impact of Geriatric Experience Training on Nurses in Preventing Falls in Elderly Patients.

Objective: This study aimed to explore the effects of geriatric experience training on nurses from multiple primary healthcare units in the context of population aging. The study also evaluated the impact of this training on improving nurses' cognitive abilities in preventing falls/bedside accidents in elderly patients and implementing safe nursing practices to reduce the incidence of falls/bedside accidents. Methods: A total of 302 nurses involved in geriatric care from 18 primary healthcare units in the region were randomly categorized into 2 groups on a 1:1 basis. The control group received regular training on falls/bedside accident prevention for patients, whereas the observation group received additional geriatric experience training along with the regular training. Further, 420 elderly patients who experienced moderate-to-severe falls/bedside accidents between February and July 2022, with a Morse Fall Scale (MFS) score of ≥25 were randomly assigned to either the observation or control group on a 1:1 basis. This study compared the 2 groups in terms of nurses' awareness of falls/bedside accident risks, incidence of falls/bedside accidents in patients and patient satisfaction with fall/bedside accident prevention care. Results: No statistically significant differences were observed (P > .05) between the 2 groups of nurses, except in their awareness of the aging population and the increased risk for falls/bedside accidents in elderly patients. However, the observation group nurses scored higher in other aspects of falls/bedside accident risk awareness after undergoing geriatric experience training (P < .05). The incidence of falls/bedside accidents was significantly lower in the observation group than in the control group (P < .05). Patient satisfaction with falls/bedside accident prevention care was significantly higher in the observation group compared with the control group (P < .05). Conclusion: Geriatric experience training for nurses in multiple primary healthcare units in the region could effectively improve the capabilities of primary hospitals in preventing falls/bedside accidents.

Identifying chemical markers in wine-processed Salvia miltiorrhiza using ultrahigh-performance liquid chromatography-quadrupole-time-of-flight-tandem mass spectrometry.

To find the chemical markers of wine-processed Salvia miltiorrhiza (WSM), 76 constituents, including diterpenoid quinones and phenolic acids in Salvia miltiorrhiza (SM) and WSM, were profiled using ultrahigh-performance liquid chromatography-quadrupole-time-of-flight-tandem mass spectrometry (UPLC-Q-TOF-MS/MS) in positive- and the negative-ion modes. Thirty compounds were screened out as candidate differential components using chemometrics analysis, and the concentration of most compounds increased after processing with wine. Seven compounds, namely tanshinone IIA, magnesium lithospermate B, salvianolic acid G, cryptotanshinone, isocryptotanshinone, salvianolic acid B, and rosmarinic acid, were selected as chemical markers of WSM using variable importance of the project. This study revealed the chemical markers of WSM and confirmed that WSM can improve the extraction and solubility effect of chemical constituents.

Lewis Acid-Promoted Oxidative Cleavage of Carbon-Carbon Bonds: Synthesis of N-Arylated Lactam-Type Iminosugars.

In this paper, a mild strategy for the oxidative cleavage of carbon-carbon bonds catalyzed by Lewis acid was developed in air condition at room temperature. Under such conditions, the bis-carbonyl compounds 3 were directly afforded from the reaction of D-ribose tosylate 1 and aniline in excellent yields through the oxidative cleavage of the key intermediate iminium-ion A and its tautomer enamine B. A series of N-arylated lactam-type iminosugars 5 were then successfully obtained by removing the isopropylidene group from 3 with the aid of the condensation agent DCC. Additionally, reduction of A and the removal of the isopropylidene group could provide N-arylated iminosugars 4. This strategy enables the oxidative cleavage of carbon-carbon bonds under mild conditions and facilitates the synthesis of the novel iminosugars with potent biological activity.

C/EBPα aggravates renal fibrosis in CKD through the NOX4-ROS-apoptosis pathway in tubular epithelial cells.

BACKGROUND: Chronic kidney disease (CKD) is a prevalent renal disorder with various risk factors. Emerging evidence indicates that the transcriptional factor CCAAT/enhancer binding protein alpha (C/EBPα) may be associated with renal fibrosis. However, the precise role of C/EBPα in CKD progression remains unexplored. METHODS: We investigated the involvement of C/EBPα in CKD using two distinct mouse models induced by folic acid (FA) and unilateral ureteral obstruction (UUO). Additionally, we used RNA sequencing and KEGG analysis to identify potential downstream pathways governed by C/EBPα. FINDINGS: Cebpa knockout significantly shielded mice from renal fibrosis and reduced reactive oxygen species (ROS) levels in both the FA and UUO models. Primary tubular epithelial cells (PTECs) lacking Cebpa exhibited reduced apoptosis and ROS accumulation following treatment with TGF-ß. RNA sequencing analysis suggested that apoptosis is among the primary pathways regulated by C/EBPα, and identified NADPH oxidoreductase 4 (NOX4) as a key protein upregulated upon C/EBPα induction (ICCB280). Treatment with l-Theanine, a potential NOX4 inhibitor, mitigated renal fibrosis and inflammation in both the FA and UUO mouse models. INTERPRETATION: Our study unveils a role for C/EBPα in suppressing renal fibrosis, mitigating ROS accumulation, and reducing cell apoptosis. Furthermore, we investigate whether these protective effects are mediated by C/EBPα's regulation of NOX4 expression. These findings present a promising therapeutic target for modulating ROS and apoptosis in renal tubular cells, potentially offering an approach to treating CKD and other fibrotic diseases.

Interpretable machine learning for predicting chronic kidney disease progression risk.

Objective: Chronic kidney disease (CKD) poses a major global health burden. Early CKD risk prediction enables timely interventions, but conventional models have limited accuracy. Machine learning (ML) enhances prediction, but interpretability is needed to support clinical usage with both in diagnostic and decision-making. Methods: A cohort of 491 patients with clinical data was collected for this study. The dataset was randomly split into an 80% training set and a 20% testing set. To achieve the first objective, we developed four ML algorithms (logistic regression, random forests, neural networks, and eXtreme Gradient Boosting (XGBoost)) to classify patients into two classes-those who progressed to CKD stages 3-5 during follow-up (positive class) and those who did not (negative class). For the classification task, the area under the receiver operating characteristic curve (AUC-ROC) was used to evaluate model performance in discriminating between the two classes. For survival analysis, Cox proportional hazards regression (COX) and random survival forests (RSFs) were employed to predict CKD progression, and the concordance index (C-index) and integrated Brier score were used for model evaluation. Furthermore, variable importance, partial dependence plots, and restrict cubic splines were used to interpret the models' results. Results: XGBOOST demonstrated the best predictive performance for CKD progression in the classification task, with an AUC-ROC of 0.867 (95% confidence interval (CI): 0.728-0.100), outperforming the other ML algorithms. In survival analysis, RSF showed slightly better discrimination and calibration on the test set compared to COX, indicating better generalization to new data. Variable importance analysis identified estimated glomerular filtration rate, age, and creatinine as the most important predictors for CKD survival analysis. Further analysis revealed non-linear associations between age and CKD progression, suggesting higher risks in patients aged 52-55 and 65-66 years. The association between cholesterol levels and CKD progression was also non-linear, with lower risks observed when cholesterol levels were in the range of 5.8-6.4 mmol/L. Conclusions: Our study demonstrated the effectiveness of interpretable ML models for predicting CKD progression. The comparison between COX and RSF highlighted the advantages of ML in survival analysis, particularly in handling non-linearity and high-dimensional data. By leveraging interpretable ML for unraveling risk factor relationships, contrasting predictive techniques, and exposing non-linear associations, this study significantly advances CKD risk prediction to enable enhanced clinical decision-making.

A Healthy, Low-Carbohydrate Diet During Pregnancy Is Associated With a Reduced Risk of Gestational Diabetes Mellitus.

CONTEXT: Evidence on the associations of low-carbohydrate diet (LCD) during pregnancy with gestational diabetes mellitus (GDM) has been limited and inconsistent. OBJECTIVE: We aimed to prospectively evaluate the risk of GDM associated with the LCD considering the quality of macronutrients. METHODS: All participants were from a prospective cohort in Wuhan, China. The overall, healthy LCD (emphasizing low-quality carbohydrates, plant protein, and unsaturated fat), and unhealthy LCD (emphasizing high-quality carbohydrates, animal protein, and saturated fat) scores were calculated according to the percentage of energy intake from carbohydrates, protein, and fat. GDM was screened by a 75-g oral glucose tolerance test between 24 and 28 weeks. Poisson regression models were used to calculate relative risks (RRs) and 95% CIs. RESULTS: Of 2337 pregnant women, 257 (11.0%) were diagnosed with GDM. Overall LCD score was not associated with risk of GDM, but the healthy and unhealthy LCD scores were associated with the risk of GDM. The multivariable-adjusted RRs (95% CI) were 0.68 (0.49-0.94) and 1.52 (1.11-2.08) for healthy and unhealthy LCD scores comparing the highest with the lowest quartile. Substituting high-quality carbohydrates for low-quality carbohydrates and animal protein, and substituting unsaturated fat for saturated fat, were associated with a 13% to 29% lower risk of GDM. CONCLUSION: A healthy LCD during pregnancy characterized by high-quality carbohydrates, plant protein, and unsaturated fat was associated with a lower risk of GDM, whereas an unhealthy LCD consisting of low-quality carbohydrates, animal protein, and saturated fat was associated with a higher risk of GDM.

Near-infrared-II Ag2S quantum dot probes targeting podoplanin enhance immunotherapy in oral squamous cell carcinoma.

Partial epithelial-mesenchymal transition (pEMT) plays a vital role in oral squamous cell carcinoma (OSCC) cervical lymph node metastasis and tumor immune escape as an immune barrier. However, targeted interventions for pEMT have yet to be established. In this study, we generated an αPDPN-Ag2S probe by modifying a Podoplanin(PDPN) monoclonal antibody on the surface of near infrared (NIR)-II Ag2S quantum dots (QDs) with carboxyl groups through an amide reaction. Then, we evaluated its in vivo targeting ability, therapeutic efficacy of eliminating pEMT using αPDPN-Ag2S-mediated NIR-II photoimmunotherapy (PIT) and biological safety. Here, we found that pEMT is related to CD8 + T-cell infiltration in our human OSCC tissue microarray. Compared with PdpnWT SCC7, the slower growth rate of subcutaneous graft tumors implanted with PdpnKD SCC7 was associated with a change in the tumor immune microenvironment (TIM) in an immunocompetent C3H/HeJ mouse model. In vitro, αPDPN-Ag2S plus NIR 808 nm laser irradiation induced SCC7 cell death. In vivo, NIR-II imaging results show that the αPDPN-Ag2S probe has a good active-targeting ability in a 4-nitroquinoline 1-oxide (4NQO)-induced C57 mouse OSCC model and C3H/HeJ SCC7 subcutaneous graft tumor model. Elimination of pEMT cells by NIR-II αPDPN-Ag2S probe-mediated PIT significantly reversed the local immunosuppressive tumor microenvironment and enhanced PD-1 immunotherapy efficacy. The safety profiles of αPDPN-Ag2S in BALB/c mice were also acceptable. Thus, αPDPN-Ag2S has important clinical translational value in predicting the risk of cervical lymph node metastasis. Importantly, our study proposed a new way to improve the efficacy of tumor immunotherapy.

Oral glucocorticoids with intravenous cyclophosphamide or oral glucocorticoids alone in the treatment of IgA nephropathy present with nephrotic syndrome and mesangioproliferative glomerulonephritis.

Background: Few studies have evaluated the treatment of immunoglobulin A nephropathy (IgAN) patients with nephrotic syndrome (NS) and mesangioproliferative glomerulonephritis (MPGN). The aim of this study was to compare the therapeutic effects of oral glucocorticoids (GCS) combined with intravenous cyclophosphamide (CTX) and oral GCS alone in the treatment of the MPGN-IgAN patients with NS. Methods: Biopsy-proven primary IgAN patients who were aged ≥14 years at diagnosis, had coexistent NS and MPGN and estimated glomerular filtration rate (eGFR) ≥15 mL/min/1.73 m2, and were treated by oral GCS combined with intravenous CTX or oral GCS alone for 6-12 months were retrospectively included. The patients in the GCS + CTX (prednisone 0.6-0.8 mg/kg/day and intravenous CTX 0.6-1.0 g monthly) or GCS (prednisone 0.8-1 mg/kg/day) group were rather matched at a 1:1 ratio on key characteristics by propensity score matching. The primary outcome was defined as either complete remission or partial remission at Month 24. The secondary outcome was a composite renal endpoint defined as a 50% decline in eGFR, doubling of serum creatinine or progression to end-stage kidney disease. Results: Among the 146 IgAN patients who met the inclusion criteria, 42 patients were enrolled in the GCS + CTX group, and 42 patients were enrolled in the GCS group after propensity score matching. The clinical and histological parameters were similar between the two groups. Remission occurred more frequently in the GCS + CTX group at Month 6 (88.1% vs 52.4%, P < 0.001), Month 12 (88.1% vs 56.1%, P = 0.001) and Month 24 (85.0% vs 47.5%, P < 0.001) than in the GCS group. Moreover, subgroup analysis revealed that the higher response rate at Month 24 in the GCS + CTX group than in the GCS group was also present in different subgroups defined by sex, age, eGFR or Oxford MEST-C. Notably, we found that eGFR decreased at a lower rate in patients from the GCS + CTX group than in patients from the GCS group [eGFR slope: 0.05(-3.09, 3.67) vs -2.56 (-11.30, 0.86) mL/min/1.73 m2/year, P = 0.03]. Based on multivariate Cox regression analysis, GCS + CTX treatment was found to be independently associated with a decrease in risk for the composite endpoint after adjusted by the International Risk Prediction Score with race (hazard ratio = 0.17, 95% confidence interval 0.04-0.83, P = .03). There was no significant difference in adverse events (50.0% vs 42.9%, P = 0.51) or serious adverse events (7.1% vs 11.9%, P = .71) between the two groups. Conclusions: Oral GCS combined with intravenous CTX is superior to GCS alone in treating MPGN-IgAN patients combined with NS. As the retrospective design and small sample size, our findings need to be validated by a prospective study.

Effects of electroacupuncture on refractory interstitial cystitis/bladder pain syndrome: A one-year follow-up case report.

BACKGROUND: Patients with interstitial cystitis/bladder pain syndrome (IC/BPS) commonly face a decline in their quality of life and social functioning upon discontinuation of conventional therapy, which is known for its limited efficacy and the risk of relapse. While the existing evidence is somewhat restricted, acupuncture is being explored as a potential and effective treatment option for IC/BPS. CASE PRESENTATION: A 67-year-old woman, diagnosed with refractory IC/BPS, underwent treatment at the Medical Acupuncture Department of Sanming Integrated Traditional Chinese and Western Medicine Hospital. She reported symptoms of lower urinary system dysfunction, including urgency, frequency, and nocturia, along with chronic pelvic pain, and a persistent feeling of pressure and discomfort lasting over 8 years. The patient's visual analog scale (VAS) score for pelvic pain was 7 points prior to receiving acupuncture treatment. Throughout the day, she had more than 10 urinations, and at night, she urinated about once per hour. The O'Leary-Sant interstitial cystitis symptom index/interstitial cystitis problem index (ICSI/ICPI) score was 34 points, and the pelvic pain and urgency frequency (PUF) score was 19 points. RESULTS: The patient's complaints were significantly alleviated after 12 sessions of electroacupuncture treatment at BL32, BL33, BL35, and SP6 over 4 weeks. The patient claimed total relief from pelvic pain, with a VAS score of 0. The patient achieved a PUF score of 4 points and an ICSI/ICPI score of 7 points. In addition, there was a significant reduction in the frequency and urgency of urination. The patient experienced a frequency of 4-5 urinations during the day and 1-2 times at night. Subsequently, the patient's mental state and sleep quality were improved. The patient's symptoms did not change at one-year follow-up. CONCLUSION: Electroacupuncture has proven to be an effective management method for IC/BPS, as evidenced by the patient's alleviated lower urinary system symptoms and reduced pelvic pain.

Trajectories of Fasting Plasma Glucose and Risks of Chronic Kidney Disease in a General Chinese Population: A Retrospective Study.

Aim: To investigate the association between longitudinal changing patterns of fasting plasma glucose (FPG), and kidney function change in the general population. Methods: We conducted a retrospective, longitudinal cohort study of a health examination center database in China. Subjects who had at least three visits from 2011 to 2018 with baseline eGFR ≥60 mL/min/1.73 m2 were enrolled. The FPG trajectories were identified by group-based trajectory modeling (GBTM). We examined the association of eGFR slopes and FPG trajectories by Cox analysis. Results: Totally, 8114 participants were identified. Three heterogeneous FBP trajectories were detected by GBTM as low-stable group (n=7294), moderate-stable group (n=657) and high-stable group (n=163). The high-stable group had lower baseline eGFR, a higher percentage of fast eGFR slope, lower HDL-c, higher LDL-c, higher cholesterol, and higher Lg(triglyceride). Cox analysis showed that the high-stable trajectory was a risk factor for fast eGFR decline (for eGFR slope <-4 mL/min per 1.73 m2 per year, adjusted HR [95% CI] 1.544 [0.876, 2.722]; for eGFR slope <-5 mL/min per 1.73 m2 per year, adjusted HR [95% CI] 2.117[1.100, 4.075]). Further, we analyzed a subgroup in which participants' long-term FPG was normal. We divided this subgroup into four trajectories by GBTM, and Cox analysis showed that after adjustment for other potential confounding factors, the high-stable trajectory was an independent risk factor for fast eGFR slope (for eGFR slope <-4 mL/min per 1.73 m2 per year, adjusted HR [95% CI] HR 1.640[1.050, 2.561]; for eGFR slope <-5 mL/min per 1.73 m2 per year, adjusted HR [95% CI] 1.818[1.018, 3.248]) in subgroup. Conclusion: We found that discrete FPG trajectories were significantly associated with risk of fast eGFR slope in individuals and those with long-term normal FPG. These observations suggest the importance of early prevention of CKD among individuals who are high-glycemic and normoglycemic.

Corn silk polysaccharides attenuate diabetic nephropathy through restoration of the gut microbial ecosystem and metabolic homeostasis.

Introduction: The pathogenesis of diabetic nephropathy (DN) is complex, inflammation is the central link among the inducing factors in the existing research, and the gutkidney axis could scientifically explain the reasons for the accumulation of chronic low-grade inflammation. As both a medicine and food, corn silk contains abundant polysaccharides. Historical studies and modern research have both confirmed its intervention effect on diabetes and DN, but the mechanism of action is unclear. Methods: In this study, a DN rat model was generated, and the therapeutic effect of corn silk polysaccharides (CSPs) was evaluated based on behavioral, histopathological and biochemical indicators. We attempted to fully understand the interactions between CSPs, the gut microbiota and the host at the systemic level from a gut microbiota metabolomics perspective to fundamentally elucidate the mechanisms of action that can be used to intervene in DN. Results: Research has found that the metabolic pathways with a strong correlation with CSPs were initially identified as glycerophosphate, fatty acid, bile acid, tyrosine, tryptophan and phenylalanine metabolism and involved Firmicutes, Bacteroides, Lachnospiraceae-NK4A136- group and Dubosiella, suggesting that the effect of CSPs on improving DN is related to changes in metabolite profiles and gut microbiota characteristics. Discussion: CSPs could be harnessed to treat the abnormal metabolism of endogenous substances such as bile acids and uremic toxins caused by changes in gut microbiota, thus alleviating kidney damage caused by inflammation. In view of its natural abundance, corn silk is safe and nontoxic and can be used for the prevention and treatment of diabetes and DN.

[An experimental study of acute toxicity and pharmacology of fermented Platycodonis Radix].

This study investigated the acute toxicity of fermented Platycodonis Radix on mice and its effect on coughing in mice infected with Mycoplasma pneumoniae. The maximum dosage(MAD) was used in the acute toxicity experiment on mice to observe the signs of mice. After 14 days, dissection, blood biochemical examination, and pathological tissue section observation were conducted. In the pharmacological experiment of fermented Platycodonis Radix, 60 healthy BALB/c mice, 30 males and 30 females, were randomly divided into a blank group, a model group, a carbetapentane group(0.013 g·kg~(-1)·d~(-1)), and high-, medium-, and low-dose fermented Platycodonis Radix groups(5.2, 2.6, and 1.3 g·kg~(-1)·d~(-1)), with 10 mice in each group. Except for the blank group, the mice in the other five groups underwent model induction by intranasally instilling 20 µL of 1×10~6 CCU M. pneumoniae for 3 days, and the mice in each group were orally administered the corresponding drugs for 7 days. Cough induction experiment was conducted to observe and record the cough latency and total cough count within 3 min for each group. Hematoxylin-eosin(HE) staining and Masson staining were used to observe the pathological changes in lung tissues. Immunohistochemistry was performed to observe the protein expression of transient receptor potential A1(TRPA1), calcitonin gene-related peptide(CGRP), and substance P(SP) in the lung tissues of mice in each group. Real-time fluorescence-based quantitative polymerase chain reaction(qRT-PCR) was used to elucidate the changes in the mRNA levels of cough-related factors TRPA1, CGRP, and SP in mice treated with fermented Platycodonis Radix. No mice died in the acute toxicity experiment, and there were no changes in general behavior and major organ histopathological examinations. Compared with the blank group, there were no statistically significant differences in blood biochemical indexes. In the pharmacological experiment of fermented Platycodonis Radix, compared with the model group, the high-and medium-dose fermented Platycodonis Radix groups showed improved lung tissue structure of mice, with clear structure and regular tissue morphology. The qRT-PCR and immunohistochemical detection showed a decrease in the expression of TRPA1, CGRP, and SP in the fermented Platycodonis Radix groups. Fermented Platycodonis Radix can exert an inhibitory effect on cough by suppressing the expression of TRPA1, CGRP, and SP in lung tissues, thereby identifying the target of the drug.

Research progress on preparation of lateral femoral tunnel and graft fixation in anterior cruciate ligament reconstruction.

Anterior cruciate ligament (ACL) injury is one of the most common types of sports injuries. People's need to participate in sports and desire for a high quality of life promotes the continuous development of ACL reconstruction technology. Arthroscopic ACL reconstruction has been recognized as an effective method for the treatment of ACL injuries. This review analyses and summarizes the advantages and limitations of each surgical procedure for arthroscopic ACL reconstruction reported in the relevant literature so as to promote the future development of more relevant techniques.

A pilot study on Paxlovid therapy for hemodialysis patients with severe acute respiratory syndrome coronavirus 2 infections.

We aimed to investigate the safety and efficacy of nirmatrelvir/ritonavir (Paxlovid) therapy for hemodialysis-dependent patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Thirteen hemodialysis patients infected with the Omicron variant of SARS-CoV-2 from April 3 to May 30, 2022, were recruited. Laboratory parameters and chest CT (computed tomography) imaging were analyzed. The treatment group included six patients who received 150 mg/100 mg of Paxlovid orally once daily for 5 days, whereas the control group included seven patients who received basic treatment. No serious adverse reactions or safety events were recorded. Four control patients progressed to moderate disease, and none in the treatment group showed progression of chest CT findings (P < 0.05). Paxlovid therapy tended toward early viral clearance and low viral load on Day 8. Moreover, 83.3% of the patients in the treatment group and 57.1% of the patients in the control group turned negative within 22 days. In the Paxlovid treatment group, we found significantly increased levels of lymphocytes (P=0.03) and eosinophils (P=0.02) and decreased levels of D-dimer on Day 8 compared with those on Day 1. Paxlovid therapy showed a potential therapeutic effect with good tolerance in hemodialysis patients. The optimal dose and effectiveness evaluation must be further investigated in a largeer cohort.

Engineered CD4 T cells expressing a membrane anchored viral inhibitor restrict HIV-1 through cis and trans mechanisms.

HIV-1 infection of target cells can occur through either cell-free virions or cell-cell transmission in a virological synapse, with the latter mechanism of infection reported to be 100- to 1,000-fold more efficient. Neutralizing antibodies and entry inhibitors effectively block cell-free HIV-1, but with few exceptions, they display much less inhibitory activity against cell-mediated HIV-1 transmission. Previously, we showed that engineering HIV-1 target cells by genetically linking single-chain variable fragments (scFvs) of antibodies to glycosyl phosphatidylinositol (GPI) potently blocks infection by cell-free virions and cell-mediated infection by immature dendritic cell (iDC)-captured HIV-1. Expression of scFvs on CD4+ cell lines by transduction with X5 derived anti-HIV-1 Env antibody linked to a GPI attachment signal directs GPI-anchored scFvs into lipid rafts of the plasma membrane. In this study, we further characterize the effect of GPI-scFv X5 on cell-cell HIV-1 transmission from DCs to target cells. We report that expression of GPI-scFv X5 in transduced CD4+ cell lines and human primary CD4+ T cells potently restricts viral replication in iDC- or mDC-captured HIV-1 in trans. Using live-cell imaging, we observed that when GPI-GFP or GPI-scFv X5 transduced T cells are co-cultured with iDCs, GPI-anchored proteins enrich in contact zones and subsequently migrate from T cells into DCs, suggesting that transferred GPI-scFv X5 interferes with HIV-1 infection of iDCs. We conclude that GPI-scFv X5 on the surface of transduced CD4+ T cells not only potently blocks cell-mediated infection by DCs, but it transfers from transduced cells to the surface of iDCs and neutralizes HIV-1 replication in iDCs. Our findings have important implications for HIV-1 antibody-based immunotherapies as they demonstrate a viral inhibitory effect that extends beyond the transduced CD4+ T cells to iDCs which can enhance HIV-1 replication.

Salt-Induced Coil-Globule Transition of Sulfonate-Modified HPAM is Affected by the Branched Chain Length.

Polymer flooding is a cheap and efficient method for tertiary oil recovery. However, the failure of partially hydrolyzed polyacrylamide (HPAM) molecules reduces the oil displacement efficiency under high salinity conditions. In this study, we modified HPAM molecules by sulfonic acid groups with different branched chain lengths, and we characterized the structures of these molecules in different salinity solutions through all-atoms molecular dynamics simulation. Compared with the acrylic group, the sulfonate group has excellent salt resistance because of its weak ability to attract cations. When using different lengths of branched linked branch sulfonates, increasing the length of the branched chain can improve the movement ability of sulfonates, so as to play a better salt resistance effect. However, excessive growth of branched chains can cause their association with each other and can lead to polymer folding. Therefore, we believe that the branched chain length of sulfonate should be moderately increased. These results are expected to provide theoretical support for the design and use of salt-resistant polymers..